EFFECTS OF POLLUTION-RELEVANT MAGNETITE NANOPARTICLES ON MAMMALIAN BRAIN CELLS

Particulate matter air pollution (PMAP) exposure is a recognised and increasingly concerning risk factor for Alzheimer’s disease (AD). Iron is an essential biometal, however, iron dysregulation is also implicated in AD pathogenesis. Iron-rich nanoparticulate matter, including metallic iron and iron oxides such as maghemite (Fe₂O₃) and magnetite (Fe₃O₄), has been associated with pathological hallmarks of AD. As nanoparticulate matter from air pollution can enter the human brain via the olfactory bulb, the biological interactions that may occur upon exposure are of growing interest, especially considering olfactory dysfunction is an early symptom of AD.
This study characterised the intracellular fate of magnetite within in vitro human brain cell models using microscopy techniques. Multi-assay cytotoxicity assessments were used to determine optimal concentrations of magnetite nanoparticles for uptake and internalisation studies via confocal and electron microscopy. Subsequently, it also characterised changes to neuronal function following magnetite exposure in the olfactory bulb in acute mouse brain slices using electrophysiology. Whole-cell patch clamp recordings of single olfactory receptor neurons and mitral cells were made in response to magnetite exposure and changes to excitability and network activity were profiled. The study provides new insight into the biological consequences of magnetite nanoparticle exposure on human brain cell cultures and olfactory bulb cell networks, in the context of the relationship between PMAP exposure and the mammalian brain.